Cyanoethylated cyclic ketones



Patented Oct. 9, 1945 CYANOETHYLATED CYCLIC KETONE Herman A. Bruson, Philadelphia, Pa., assignor to The Resinous Products & Chemical Company, Philadelphia, Pa., a corporation of Delaware No Drawing. Original application April 19, 1941, Serial No. 389,332. Divided and this application June 13, 1941, Serial No. 397,865

3 Claims.

This invention relates to cyclic ketones having at least one p-cyanoethyl radical on a. carbon atom adjacent to the carbonyl group of the cycle. More particularly it relates to poly-p-cyanoethylated cyclic ketones of the above type.

This invention is a division of my copending application, Serial No. 389,332, filed April '19, 1941.

According to this invention, acrylonitrile is reacted in the presence of an alkaline condensing agent with a cyclic ketone having an active methylene or methenyl group immediately adjacent to its carbonyl group. By the reaction, a p-cyanoethyl radical becomes attached to the carbon atom adjacent to the carbonyl group. If more than one active hydrogen is present'on this carbon atom, then more than one cyanoethyl group may be introduced.

Among the alkaline condensing agents which have been found efiective for promoting the reaction are the oxides, hydroxides, hydrides, amides, and alcoholates of the alkali metals or the alkali metals themselves. There may also be used other strongly basic non-metallic hydroxides such as the quaternary ammonium hydroxides. Of these, a particularly effective product is the aqueous solution containing 40% of trimethyl benzyl ammonium hydroxide which is available commercially under the trade name Triton B. One or several of these materials are suspended or, preferably, dissolved in the ketone itself or in a solution of the ketone in an inert liquid, such as dioxane, ether, or benzene, or in a, liquid which is less reactive than the reacting ketone, such as water, or tertiary butyl alcohol.

The quantity of alkaline condensing agent required is usually relatively small, amounts of the order of 1% to 10% on the combined weight of the reactants usually being sufficlent. Since the condensation ceases if the alkali is depleted byside reactions or impurities of an acid nature in the startingmaterials, it is advantageous to test the reaction mixture for alkalinity toward red litmus from time to time during the condensation and, if an alkaline reaction is no longer shown, to add more alkali to make up for the loss.

The reaction is applicable to a wide variety of monocyclic or polycyclic ketones of the cycle aliphatic, hydroaromatic or heterocyclic series, including saturated or unsaturated monoketones or poly-ketones. The ketones may contain other functional groups than the carbonyl p, so long as they do not readily destroy the alkaline condensing agent used. For example,

Among the more readily available typical cyclic-ketones, having reactive hydrogen atoms ortho to the carbonyl groups which are suitable for the purpose of this invention, may be mentioned the following: Cyclopentanone, cyclohexanone, p-phenyl cyclohexanone, 0-, m-, or pv methyl cyclohexanone, menthone, p-ter-butyl cyclohexanone. p-ter-amyl cyclohexanone, pter-octyl cyciohexanone, o,p-di-tertiary amyl cyclohexanone, p-benzyl cyclohexanone, p-cyclohexyl-cyclohexanone, cyclohexenones, aor 5- tetralone, cholestanone, 2,2,5,5-tetramethyltetrahydro furanone 3,N-methyl-triacetone-' about 0., although initial temperatures of 25 C. to 60 C. are preferred. The reaction is usually exothermal, so that cooling, at least during the early part of the condensation, is generally advantageous in order to control the vigor of the reaction and to prevent undesired polymerization or side reactions. In'this connection it is sometimes desirable to add polymerization inhibitors, such as hydroquinone, alpha-naphthol, catechol, finely divided copper compounds, or sulfur.

In general, cyclic ketones having the carbonyl between two -CH2- groups, as in cyclopentanone, cyclohexanone, and their metaor parasu-bstituted homologues, readily take up as many as four mols of acrylonitrile as follows:

N'CCHIOH: o0 omomoN Nccnaonl cmomcn whereas a monoortho-substituted cyclic ketone, as for example o-methyl cyclohexanone, takes up as many as three mols of acrylonitrile Ncomcm co cmcmon cm omomcN Finally, ketones such as a-tetralone or e-hydrindone, which possess only two, reactive ortho hydrogen atoms, take up to two mols of acrylonitrile.

The p-cyanoethylation products obtainable by the present process are all new compounds. They are useful as intermediate for the preparation .of monocarboxylic or polycarboxylic acids, amides,

esters, amines, or polyamines, amidines, amino acids, amino alcohols, or thio-amides by the reactions characteristic of the nitrile group. Many of the compounds may find uses in diverse fields,

strong bases may be used.

Example 1 To a solution of 42 g. of cyclopentanone (0.5

mol) in 200 g. of benzene, there was added g.

of an aqueous 40% solution of trimethyl benzyl ammonium hydroxide. The mixture was stirred and cooled to 35-45 C., while 106 g.' of acrylonitrile (2 mols) was added dropwise during 1 hours. grystals began to separate within afew minutes after the addition was begun. As the reaction proceeded, it was necessary to add 200 cc. of benzene to prevent clogging of the stirrer by the crystalline mass. The mixture was allowed to stand for 18 hours before the crystals were filtered by suction. The yield was 144 g. or 97.3% of theory. The product can be recrystallized from hot methyl ethyl ketone or glycol monoethyl ether (Cellosolve) from which it separates in colorless crystals, melting, when pure, at 175 C. Its analysis corresponds to tetra (fl-cyanoethyl) -cyclopentanone, having the formula Nccmcm co omomcN Ncc'nlcni l Jjcmcmcrr Hr Hi It is only very slightly soluble in benzene, toluene, dioxane, or water.

Upon boiling the above product with an excess of aqueous sodium hydroxide for four hours,

the nitrile groups are quantitatively hydrolyzed and, upon acidification of the solution and cooling, there is obtained the corresponding tetra-(B-carboxy-ethyl) -cyclopentanone CHr-C(CH|CH2C 0 OH):

=0 Hr!) (CHICHIC O OH):

which may be recrystallized from water and forms colorless crystals melting at 173 C.

' Example 2 Acrylonitrile (24.4 g.) was added dropwise to a stirred solution consisting of 50 g. of dioxane, 3 g. of aqueous 40% trimethyl benzyl ammonium hywas 41 g. of colorless crystals. Upon recrystallization from ethyl alcohol, the compound formed colorless needles melting at 153 C., having the formula 7 CHrCHrCN o o--c crncmcN CHI/ Example 3 21.2 g. of acrylonitrile was added at room temperature to a mixture of 29.2 g. of a-tetralone, 50 g. of dioxane, and 4 g. of aqueous 40% trimethyl benzyl ammonium hydroxide solution. The mixture was stirred for 24 hours, then neutralized with dilute hydrochloric acid, washed with water and distilled in vacuo. The fraction boiling at 250-260 C./1 mm. formed a pale yellow oil which gradually solidified to a waxy crystalline mass. After recrystallization from ethanol, the product for-med colorless crystals melting at 0., having the formula CHzCHzCN Hg CHgCHaCN Example 4 To 935 g. of tertiary butanol there was added 15 g. of aqueous 40% potassium hydroxide solution and 294 g. of cyclohexanone (3 mols) The solution was stirred in a vessel surrounded by run ning water, and 636 g. of acrylonitrile (12 mols) added dropwise thereto during 1 /2 hours, while the temperature was maintained between 35 and 45 C. During the addition crystals separated. The mixture was stirred for an additional 15 hours at 25 C. to complete the reaction. The crystals were then filtered off, washed'with 1 liter of cold water, and dried. The yield was 820 g. of faintly yellow crystalline product or 88% of theory. Upon recrystallization from acetone, the compound forms colorless fine needles, melting when pure at 0. Its analysis corresponds to tetra-(fi-cyanoethyl)-cyclohexanone having the formula CHrCHrCN NC CHzCHa CHQCHICN impurities.

crystals upon acidifying the reaction mixture with hydrochloric acid. Upon recrystallization from hot water,- it forms colorless crystals melting at l'l9180 C.

' Example To a rapidly stirred mixture of 98 g. of cyclohexanone (1 mol) and 5 g. of aqueous 40% trimethyl benzyl ammonium hydroxide, 53 g. of acrylonitrile (1 mol) was added dropwise during 1% hours while the reaction temperature was maintained at 30-35 C. by external cooling. After the addition, the mixture was stirred for one hour at 35 C. and then at 25 C. for 18 hours. The reaction mixture was acidified with dilute hydrochloric acid and the crystalline tetra-(pcyanoethyl) -cyclohexanone (30 g.) filtered ofi. The filtrate was then distilled in vacuo. A colorless 011 (16.5 g.) distilled over at 138-142 C./ mm., consisting of mono-(p-cyanoethyl)-cyclohexanone.

C CH-CHiCHrCN At 195-l98 C./l-mm., a second fraction (13 g.) distilled over as a very viscous, pale yellow oil which gradually crystallized on standing. After recrystallization from benzene, it formed colorless crystals melting at 69.5 0. Its analysis showed it to be a di-(p-cyanoethyl) -cyclohexanone,

Example 6 To a stirred mixture consisting of 5 g. of aqueous 40% trimethyl benzyl ammoniiun hydroxide, 200 g. of benzene and 44.8 g. of ortho-methylcyclohexanone there was added dropwise 63.5 g. of acrylonitrile while the reaction temperature was maintained at 30-40" C. by cooling. The mixture was stirred thereafter for 18 hours at 25 C., neutralized with dilute hydrochloric acid, washed thoroughly with water, filtered, and distilled in vacuo. The main fraction (103 g.) distilled at 275-285" C./1 mm., as a'pale reddish syrup consisting essentially of tri-(p-cyanoethyl) -o-methyl-cyclohxanone NCCHzCEB L Example 7 To a solution of 45.6 g. of ortho-methallylcyclohexanone, 100 g. of benzene, and 3 g. of aqueous 40% trimethyl benzyl ammonium hydroxide there was added dropwise with rapid stirring while the mixture was cooled to 30-40 C. 47.7 g. of acrylonitrile during a period of 45 minutes. The mixture was then stirred at room temperature for two hours and finally heated on a water bath at 50 C. for 2 hours. The product was washed with water containing a little hydrochloric acid to destroy the alkali, and the washed oil layer was filtered to remove polymeric The filtrate was then distilled in vacuo. The main fraction boiled between 230 and 270 C./1-3 mm. and formed a pale reddish cniomoN l CHnCHzCN oil consisting essentially of tri-(fi-cyanoethyD- methallyl-cyclohexanone.

ll NocmoH, c omcmcN to 28-40 C. The mixture was stirred thereafter for 24. hours at room temperature, acidified with dilute hydrochloric acid, taken up in ethylene dichloride and the ethylene dichloride solution thoroughly washed with water and separated. Upon evaporation of the solvent under reduced pressure there remained 189 g. of a dark, viscoussyrup. Upon distillation invacuo, this yielded a pale reddish oil, boiling at 295-300 C./1 mm., consisting of tri-(p-cyanoethyl)-menthone.

II NC CHsCH: C

CHaCHsCN Example 9 To a solution of 51 g. of p-methyl cyclohexanone, 120 g. of tertiary butanol and 5 g. of aqueous 40% trimethyl benzyl ammonium hydroxide there was added dropwise 96.5 g. of acrylonitrile during a two-hour period, while the reaction mixture was stirred and'cooled to 38-40 C. The

' mixture was stirred for four hours after the addition had been made, and was then neutralized with dilute hydrochloric acid. The crystalline product was filtered off and washed with a little ethyl alcohol. The yield was 134.5 g. or 91% of theory. The product may be recrystallized from glycol monoethyl ether (Cellosolve) and forms colorless crystals melting at 138.5 C. Its analysis corresponds to tetra-(,e-cyanoethyl) p-methyl-cyclohexanone, having the formula 0 t NCCHICHB I l CHsCHsCN OH: H:

NC CHzCHK CHaCHiCN p-methyl cyclohexanone is obtained as a colorless crystalline compound melting at 205-206? C.

Example 10 Acrylonitrile g.) was added dropwise during one hour to astirred solution of 67 g. of paratertiary-amyl cyclohexanone, g. of dioxane, and 5 g. of aqueous 40% trimethyl benzyl ammonium hydroxde while the reaction mixture was cooled to 30-40 C. The mixture was stirred for five hours thereafter at. room temperature.

It was then acidified with dilute hydrochloric CH: "CHIOHQCN oHr-c-cmcrncN momcN I Example 11 To a solution of 63 g. of p-a,a,' -tetramethylbu-tylcyclohexanone 0.3 mol) in 100 g. of dioxane there was added 3 g. of an aqueous 40% solution of trimethyl benzyl ammonium hydroxide. The mixture was stirred and cooled to 30-40 C., while 68.6 g. of acrylonitrile (1.2 mols) was added dropwise thereto during 1 hours. The mixture'was stirred for about one hour longer at room temperature (25-30" C.) and was then warmed to 43 C. for two hours. It was cooled, acidified with dilute hydrochloric acid and washed with water. a steam bath under reduced pressure. When cold, it formed a pasty, crystalline mass weighing 118 g'. The product can be recrystallized from boiling methanol. It separates in colorless needles melting, when pure, at 155-l56 C. Its analysis corresponds to tetra-(fl-cyanoethyD- ter-octyl-cyclohexanone having the formula CHr-CHr- C cmcmcN CH; CH, 011,- CH,OH;CN CHr-JZ-CHg- CH:C :0 1

([3113 H: CH2C--CH:CH:CN

HICHzCN Example 12 Acrylonitrile (97.5 g.) was added dropwise dur- The oil was then dried on v ing one hour to a stirred solution of 83 g. of para-cyclohexyl-cyclohexanone, 150 g. 'of dioxane, and g. of aqueous 40% trimethyl benzyl ammonium hydroxide 'while the reaction mixture was cooled to 30-38 C. The mixture was stirred thereafter for three hours, then acidified with dilute hydrochloric acid, taken up in ethyli I ene dichloride, washed with water, and the ethylene dichloride layer evaporated to dryness under reduced pressure on a steam bath. The residue weighed g. and formed a soft, sticky, resinous mass. Upon stirring this mass with hot m'ethanol, it crystallized and was filtered hot. The crystalline product, upon recrystallization from glycol monoethyl ether, separated in colorless crystalsmelting, when pure, at 2-23-224 C., having the formula crncrncN GHQ-CH: CHz- -CH2CH:CN

c CHO c=o cH,c cure-eugenics:

mcmcN I claim:

1. A method for the p-cyanoethylation of a cyclic ketone havingat least one hydrogen atom on a carbon atom adjacent to the carbonyl group of the cycle, which comprises condensing acrylonitrile with said cyclic ketone in the presence of a strongly basic quaternary ammonium hydroxide.

2. A method for the p-cyanoethylation of an alicyclic ketone having at least one hydrogen atom on a carbon atom contiguous to the carbonyl group of the cycle, which comprises condensing acrylonitrile with said alicyclic ketone in the presence of a strongly basic quaternary ammonium hydroxide.

3. A method for the fl-cyanoethylation of an alicyclic ketone having at least one hydrogen atom on a carbon atom contiguous to the carbonyl group of the cycle, which comprises condensing acrylonitrile with said alicyclic ketone in the presence of trimethyl benzyl ammonium hydroxide.

- HERMAN A. BRUSON. 

